Diisopropylamine → Ethyl 8-nitro-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydroquinoline-3-carboxylate

HRID 520459ノート

反応式

HRID 520459 の反応式
C(NC(C)C)(C)C.[Li]CCCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[N+:19]([C:22]1[C:27]2[N:28]=[C:29]([C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=3)[O:30][C:31](=O)[C:26]=2[CH:25]=[CH:24][CH:23]=1)([O-:21])=[O:20].[Li+].CC([N-]C(C)C)C.CCOC(C)=O.[OH-].[Na+]>C1COCC1.[Cl-].[Na+].O>[N+:19]([C:22]1[CH:23]=[CH:24][CH:25]=[C:26]2[C:27]=1[NH:28][C:29]([C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:40])([F:41])[F:42])[CH:34]=1)=[C:14]([C:13]([O:16][CH2:17][CH3:18])=[O:15])[C:31]2=[O:30])([O-:21])=[O:20]

参加物

9

反応物 6

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 585528458-nitro-2-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-4-oneHCID 86660235LDA EtOAcHCID 178418339Butyllithium

生成物 1

HCID 58552877Ethyl 8-nitro-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydroquinoline-3-carboxylate収率 42%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 57417360Sodium chloride; water溶媒

反応条件

温度
-78 °C

実験手順

A solution of diisopropylamine (7.00 mL, 50.0 mmol) in THF (100 mL) was cooled to −78° C., and n-BuLi (20.0 mL, 2.5 M in hexanes, 50.0 mmol) was added. After stirring for 20 min at −78° C., ethyl acetate (5.72 mL, 58.6 mmol) was added. The solution was stirred at −78° C. for 10 min, warmed to 0° C. and stirred for 10 min, then cooled back to −78° C. A solution of 8-nitro-2-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-4-one 3 (9.85 g, 29.3 mmol) in THF (100 mL) was added over 5 min to the LDA/EtOAc mixture. The reaction was stirred at −78° C. for 1 h, then warmed to room temperature over 2 h. 1N NaOH (50 mL) was then added, and the reaction stirred vigorously overnight. Brine (50 mL) was added, and the organic layer separated. The aqueous layer was extracted with ethyl acetate (2×100 mL), and the combined organic layers dried with MgSO4 and concentrated under reduced pressure. The remaining material was purified by MPLC (using a gradient of 20% to 50% EtOAc in pentane) to give 36 (5.00 g, 42% yield).

後処理

  1. stirringThe solution was stirred at −78° C. for 10 min
  2. temperaturewarmed to 0° C.
  3. stirringstirred for 10 min
  4. temperaturecooled back to −78° C
  5. stirringThe reaction was stirred at −78° C. for 1 h
  6. temperaturewarmed to room temperature over 2 h
  7. stirringthe reaction stirred vigorously overnight
  8. customthe organic layer separated
  9. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  10. dry with materialthe combined organic layers dried with MgSO4
  11. concentrationconcentrated under reduced pressure
  12. customThe remaining material was purified by MPLC (

出典と根拠

ORDレコード
ord-6644696c027542ec97b0f176c4d34f3b
出典データセット
uspto-grants-2016_05
特許番号
US09326986B2

反応ノート

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